Chaihu-Shugan-San Reinforces CYP3A4 Expression via Pregnane X Receptor in Depressive Treatment of Liver-Qi Stagnation Syndrome

Abstract

Backgrounds. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Aim of the Study. From traditional Chinese medicine and pharmacogenetics perspectives, the present study aimed to investigate the antidepressant effects of CSS on a mouse model of Liver-Qi Stagnation (LQS) syndrome and its underlying mechanisms. Methods and Materials. We used two main mouse models of depressive syndromes in the study, including LQS and liver stagnation and spleen deficiency (LSSD) syndrome. Tail suspension and forced swimming tests were used to evaluate the effects of CSS on animal behaviour. The expression level of the CYP450 enzyme from liver microsomes was analysed by western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). More specifically, we analysed the key compounds of CSS that are responsible for CYP450 regulation via bioinformatics. Ultimately, luciferase assays were employed to confirm the prediction in vitro. Results. CSS remarkably reduced the immobile time in LQS rather than in LSSD mice. Although CSS significantly upregulated CYP2C9 in mice with both syndromes, activated translation of CYP3A4 induced by CSS was only observed in the LQS group. Bioinformatics analysis revealed that the unique regulation of CYP3A4 was responsible for the effects of glycyrrhetinic acid (GA) from CSS. Further luciferase assays confirmed the enhancement of CYP3A4 expression via the pregnane X receptor (PXR) pathway in vitro. Conclusions. CSS specifically upregulates the translation of CYP3A4 via the PXR pathway in depressed LQS mice. GA, a bioactive compound that originates from CSS, contributes to this activation. This work provides novel insight into Chinese syndrome-based therapy for depression.

Potential Molecular Mechanisms of Chaihu‐Shugan‐San in Treatment of Breast Cancer Based on Network Pharmacology

“…Among them, gallic acid (source: Shaoyao), oxidized paeoniflorin (source: Shaoyao), paeoniflorin (source: Shaoyao), paeoniflorin (source: Shaoyao), glycyrrhizin (source: Gancao), naringin (source: Chenpi, Zhiqiao), hesperidin (source: Chenpi, Zhiqiao), and ferulic acid (source: Chuanxiong) had higher contents, all above 1000 mg/g [ 28 ]. Although some studies have comprehensively elucidated the treatment of depression [ 6 , 29 ], nonalcoholic fatty liver disease [ 30 , 31 ] and functional dyspepsia [ 5 ] by Chaihu-Shugan-San, no studies have comprehensively elucidated the mechanism of Chaihu-Shugan-San in the treatment of breast cancer. Therefore, with the aid of network pharmacology, this study analyzed the specific molecular mechanism of Chaihu-Shugan-San in the treatment of breast cancer from a microscopic perspective.…”

“…It has the effect of soothing “Liver-Qi.” It has a history of 485 years and is widely used in clinical practice [ 3 – 5 ]. Chaihu-Shugan-San includes seven kinds of traditional Chinese medicine such as Bupleurum chinense DC (Chinese name: Chaihu), Radix Paeoniae Alba (Chinese name: Baishao), Citrus reticulata Blanco (Chinese name Chenpi), Cyperus rotundus L (Chinese name: Xiangfu), Glycyrrhiza uralensis Fisch (Chinese name: Gancao), Citrus aurantium L (Chinese name: Zhiqiao), and Ligusticum chuanxiong Hort (Chinese name: Chuanxiong) [ 6 ]. Traditional Chinese medicine meridian tropism is one of the core components of the theory of TCM.…”

A Comparison Study of Chaihu Shugan San and Fluoxetine on Antidepression and Regulating Blood Rheology Effects with Chronic Restrained Stress Rats

“…e Antidepressant Effect of CHSGS and Fluoxetine. CHSGS is an effective compound formula for clinical treatment of liver Qi stagnation syndrome [14] and depression [29] in TCM. Fluoxetine is one of the commonly used medicines for depression in western medicine [17].…”

“…CHSGS is composed of Chaihu, Chenpi, Chuanxiong, Xiangfu, Zhiqiao, Shaoyao, and Gancao, and is the representative formula in the treatment of liver Qi stagnation syndrome by improving the depression state of liver Qi stagnation syndrome [14]. Fluoxetine is a selective serotonin reuptake inhibitor, which is widely used in the treatment of depression [15].…”

<p>Traditional Chinese Medicine Jiuwei Zhenxin Granules in Treating Depression: An Overview</p>

“…Animal experiments show that Chaihu Shugan San can lessen clinical symptoms and has an obvious therapeutic effect on depression in rats. [143][144][145][146] Xiao Chaihu decoction comes from the "Treatise on Febrile Diseases" and acts to reconcile Shaoyang and regulate the stomach; it is often used to treat liver stagnation and poor vitality. Xiao Chai Hu decoction can promote the recovery of BDNF levels, improve levels of neurofunctional factors, and enhance sleep quality.…”